Nabilone is the generic name assigned to 6a,10a-trans-1-hydroxy-3-(1,1-dimethylheptyl)-6,6-dimethyl-6,6a,7,8,10,10a -hexahydro-9H-dibenzo[b,d]pyran-9-one. Nabilone is among a group of trans-hexahydrodibenzopyranones which recently have been found to be particularly useful in the treatment of anxiety, depression and related disorders of the central nervous system; see U.S. Pat. Nos. 3,928,598, 3,944,673 and 3,953,603. In view of the potential clinical usefulness of nabilone and related dibenzopyranones, an extensive effort has been devoted to finding improved and alternative methods for the preparation of such compounds.
The original synthesis of 6a,10a-trans-hexahydrodibenzopyranones suffered from being multistep and of low overall yields, in addition to providing substantial mixtures of 6a,10a-cis and 6a,10a-trans isomers, the separation of which is somewhat difficult; see U.S. Pat. No. 3,507,885. A number of relatively simple one-step syntheses of 6a,10a-cis-hexahydrodibenzopyranones recently have been discovered and are summarized by Archer, et al., J. Org. Chem., 42, 2277 (1977). While a one-step synthesis of 6a,10a-trans-hexahydrodibenzopyranones from relatively simple and inexpensive starting materials has not yet been discovered, a method for conveniently converting the 6a,10a-cis isomers to the corresponding 6a,10a-trans isomers is available; see U.S. Pat. No. 4,054,582.
An object of this invention is to provide an alternative process for preparing 6a,10a-cis-hexahydrodibenzopyranones, which compounds are intermediates in the preparation of the more biologically active 6a,10a-trans isomers, e.g., nabilone.